scholarly journals Tall cell papillary thyroid carcinoma: new diagnostic criteria and mutations in BRAF and TERT

2015 ◽  
Vol 22 (3) ◽  
pp. 419-429 ◽  
Author(s):  
Matthias S Dettmer ◽  
Anja Schmitt ◽  
Hans Steinert ◽  
David Capper ◽  
Holger Moch ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Diagnostic Criteria ◽  
Adverse Outcome ◽  
Braf V600e ◽  
Molecular Diagnostic ◽  
Papillary Thyroid ◽  
Tumor Relapse ◽  
Tall Cell ◽  
Promoter Mutations

The tall cell (TC) variant of papillary thyroid carcinoma (PTC) has an unfavorable prognosis. The diagnostic criteria remain inconsistent, and the role of a minor TC component is unclear. Molecular diagnostic markers are not available; however, there are two potential candidates:BRAF V600Eand telomerase reverse transcriptase (TERT) promoter mutations. Using a novel approach, we enriched a collective with PTCs that harbored an adverse outcome, which overcame the limited statistical power of most studies. This enabled us to review 125 PTC patients, 57 of which had an adverse outcome. The proportion of TCs that constituted a poor prognosis was assessed. All of the tumors underwent sequencing forTERTpromoter andBRAFV600Emutational status and were stained with an antibody to detect theBRAFV600Emutation. A 10% cutoff for TCs was significantly associated with advanced tumor stage and lymph node metastasis. Multivariate analysis showed that TCs above 10% were the only significant factor for overall, tumor-specific, and relapse-free survival. Seven percent of the cases had aTERTpromoter mutation, whereas 61% demonstrated aBRAFmutation. The presence of TC was significantly associated withTERTpromoter andBRAFmutations.TERTpredicted highly significant tumor relapse (P<0.001). PTCs comprised of at least 10% TCs are associated with an adverse clinical outcome and should be reported accordingly.BRAFdid not influence patient outcome. Nevertheless, a positive status should encourage the search for TCs.TERTpromoter mutations are a strong predictor of tumor relapse, but their role as a surrogate marker for TCs is limited.

scholarly journals TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma

2015 ◽  
Vol 172 (4) ◽  
pp. 403-413 ◽  
Author(s):  
Greta Gandolfi ◽  
Moira Ragazzi ◽  
Andrea Frasoldati ◽  
Simonetta Piana ◽  
Alessia Ciarrocchi ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Direct Sequencing ◽  
Distant Metastases ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Mutational Status ◽  
Metastatic Behavior ◽  
Well Differentiated ◽  
Promoter Mutations

ObjectiveTranscriptional activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were reported at high frequency in aggressive poorly differentiated and anaplastic thyroid cancers. By contrast, the relevance of these mutations in the metastatic behavior of well-differentiated thyroid cancer is still to be defined. The aim of this work was to investigate the frequency ofTERTpromoter mutations in a remarkable cohort of well-differentiated papillary thyroid carcinoma that developed distant metastases (DM-PTCs) and to establish whether these mutations may be predictive of metastatic behavior.DesignWe analyzed the frequency ofTERTpromoter mutations in a group of 43 highly aggressive DM-PTCs. As controls, we analyzed these mutations in a group of 78 PTCs without distant metastases (control-PTCs). The possible correlation betweenTERTpromoter mutations and BRAF V600E mutation was also investigated.MethodsTERTpromoter mutational status was evaluated by direct sequencing of the hotspot harboring the C228T and the C250T mutations.ResultsIn the overall cohort of 121 PTCs analyzed, 17% of cases (21/121) carried a mutation in theTERTpromoter. Noticeably, 33% of DM-PTCs were mutated in theTERTpromoter while only 9% of the control-PTCs showed a mutation in this locus. We also observed a positive association between BRAF V600E andTERTC228T mutations in the cohort of DM-PTCs.ConclusionsThese results indicate thatTERTpromoter mutations are associated with the development of distant metastases in PTCs and may help in predicting aggressive behavior in this type of tumor.

scholarly journals BRAF V600E Immunoexpression in Papillary Thyroid Carcinoma and Its Association with Prognostic Factors and Histopathologic Variant

Medicinus ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. 12
Author(s):  
Erna Kristiani ◽  
Endang SR Hardjolukito ◽  
Agnes S Harahap ◽  
Benyamin Makes
Keyword(s):  
Prognostic Factors ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Clinicopathological Characteristics ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Tall Cell Variant ◽  
Tall Cell ◽  
Cell Variant

<p><strong>Aim: </strong>to provide additional information regarding the clinicopathological characteristics of Papillary Thyroid Carcinoma (PTC). Methods: Fifty patient with PTC were reviewed to determine prognostic factors such as age, gender, size of tumor and histologic variant. BRAF V600E mutation was detected by immunohistochemical staining and assessed with H score. Result: BRAF V600E mutations were detected in 17 (34%) cases. There were seven cases with extrathyroidal extension (ETE) p 0,04, 11 cases with lymph node metastasis (LNM) p &lt; 0,001, and 8 cases with tall cell variant p 0,047.The cases with positive BRAF V600E mutation had mean age of 44.71 years, and the size of the tumor between 0.1-4cm. Six cases of them are male and 11 female.</p><p><strong>Conclusion:</strong> There were significant relationships between BRAF V600E mutation with ETE, LNM, and tall cell variant. There was no significant relationship between BRAF V600E mutation, either with age, gender, or size of the tumor. BRAF V600E immunohistochemical examination can be performed as additional investigation for PTC patients.</p>

scholarly journals The prognostic significance of tall cells in papillary thyroid carcinoma: A case-control study

Tumor Biology ◽  
2018 ◽  
Vol 40 (7) ◽  
pp. 101042831878772 ◽  
Author(s):  
Sebastian Stenman ◽  
Päivi Siironen ◽  
Harri Mustonen ◽  
Johan Lundin ◽  
Caj Haglund ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Adverse Outcome ◽  
Prognostic Significance ◽  
World Health ◽  
Papillary Thyroid ◽  
Cell Composition ◽  
Tall Cell Variant ◽  
Tall Cell ◽  
Cell Variant

The subtype of the papillary thyroid carcinoma tall-cell variant has a worse prognosis than does the conventional papillary type (papillary thyroid carcinoma). The new World Health Organization 2017 classification defines a tall-cell variant as a tumour consisting of over 30% of cells that are two or three times as tall as they are wide. However, thresholds have differed. Our aim was to study how tall cells affect the prognosis of papillary thyroid carcinoma patients and to determine, for such cells, a cut-off percentage. Our cohort included 65 papillary thyroid carcinoma patients who underwent surgery at Helsinki University Hospital between 1973 and 1996: originally, 36 otherwise-matched patient pairs, eventually comprising 34 patients with an adverse outcome plus 31 who had recovered. All samples were digitally scanned and scored by two investigators based on tall cell composition. The cohort was analysed with four tall cell thresholds: 10%, 30%, 50% and 70% with a median follow-up of 22 years. In survival analysis, only the 70% threshold showed a correlation with reduced overall survival, disease-specific survival and relapse-free survival. A correlation also emerged with death from papillary thyroid carcinoma. In multivariate analysis, a 70% cut-off and age at diagnosis significantly affected DSS. Increasing tall cell score correlated with increasing age and extrathyroidal extensions. A tall cell composition of 10%, 30% or 50% showed no correlation with adverse outcome and suggests that the choice of pathologists reporting tall-cell variant should be a 70% threshold.

scholarly journals BRAF V600E and TERT Promoter Mutations in Papillary Thyroid Carcinoma in Chinese Patients

PLoS ONE ◽  
2016 ◽  
Vol 11 (4) ◽  
pp. e0153319 ◽  
Author(s):  
Jian Sun ◽  
Jing Zhang ◽  
Junliang Lu ◽  
Jie Gao ◽  
Xinyu Ren ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Chinese Patients ◽  
Papillary Thyroid ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

scholarly journals Cytologic, histologic and molecular findings of papillary thyroid carcinoma variants, one institution’s experience

2019 ◽  
Vol 9 (2) ◽  
pp. 32
Author(s):  
Nadja K. Falk ◽  
Swarnamala Ratnayaka ◽  
Andrew Sholl ◽  
Krzysztof Moroz ◽  
Tatyana Kalinicheva
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Follicular Variant ◽  
Tert Promoter Mutations ◽  
Patient Prognosis ◽  
One Year ◽  
Promoter Mutations ◽  
Worse Prognosis

Papillary thyroid carcinoma (PTC) has two major types, classic (PTCC) and follicular variant (FVPTC), which correlate with molecular findings and have varying clinical implications. We assessed the cytologic findings and subsequent surgical pathology findings with the molecular mutations in these two groups, including microcarcinomas. Fourty-four patients with PTC resections over a one-year period were retrospectively examined in conjunction with previous cytologic diagnoses. BRAF, NRAS and TERT promoter mutations for the resected specimens were analyzed. Correlation with previous cytology in regard to molecular mutations and tumor size (microcarcinoma) were made. Significantly more BRAF V600E mutations were seen with PTCC, whereas significantly more NRAS mutations were seen with FVPTC. TERT mutations were only seen with PTCC. Molecular studies for thyroid carcninomas are becoming increasingly more common and influence treatment and patient prognosis. BRAF and or TERT mutations are associated with a worse prognosis. NRAS mutations associated with FVPTC and may lead to milder cytologic changes compared to the BRAF- and TERT-driven PTCC.

Mixed histiocytosis with BRAF (V600E) mutation and papillary thyroid carcinoma

2019 ◽  
Author(s):  
Francoise Archambeaud ◽  
Pauline Vital ◽  
Gilles Russ ◽  
Isabelle Pommepuy ◽  
Julien Haroche ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
Papillary Thyroid

BRAFV600E MUTATION IN PAPILLARY THYROID CARCINOMA. CLINICAL AND METHODOLOGICAL ASPECTS

2019 ◽  
Vol 65 (1) ◽  
pp. 16-26
Author(s):  
Pavel Rumyantsev ◽  
Petr Nikiforovich ◽  
Andrey Poloznikov ◽  
Andrey Abrosimov ◽  
Vladimir Saenko ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Kinase Inhibitors ◽  
Anaplastic Carcinoma ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Wide Range ◽  
Methodological Aspects

Mutation BRAFV600E is highly specific for papillary thyroid carcinoma. It’s detected in 40-70% of all papillary thyroid carcinoma cases. Moreover this mutation is noticed in anaplastic carcinoma in 40-50%.This fact gives a chance to select patients and provide targeted therapy with multi-kinase inhibitors in cases of unresectable anaplastic carcinoma. The influence of BRAF V600E mutation for response to radioactive iodine therapy requires more evidence-based research. Existing methods for determining the BRAFV600E mutation have different accuracy, availability and cost. Other methodological aspects are also associated with the sample preparation of biological material, the quality of reagents, and the cross-validation of research results. In this review, on the basis of our own experience and literature data, the indications for determining the mutation of the BRAFV600E gene in clinical practice are refined, and a comprehensive comparative analysis of modern research methods has been conducted. This review is focused on a wide range of specialists of different types: oncologists, endocrinologists, radiologists, pathologists, and biologists.

scholarly journals Analysis of the Role of FRMD5 in the Biology of Papillary Thyroid Carcinoma

2021 ◽  
Vol 22 (13) ◽  
pp. 6726
Author(s):  
Agata M. Gaweł ◽  
Maciej Ratajczak ◽  
Ewa Gajda ◽  
Małgorzata Grzanka ◽  
Agnieszka Paziewska ◽  
...  
Keyword(s):  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Endocrine System ◽  
Metastatic Potential ◽  
Multidrug Resistant ◽  
Thyroid Tumor ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Spheroid Formation

Background: Thyroid carcinoma (TC) is the most common endocrine system malignancy, and papillary thyroid carcinoma (PTC) accounts for >80% of all TC cases. Nevertheless, PTC pathogenesis is still not fully understood. The aim of the study was to elucidate the role of the FRMD5 protein in the regulation of biological pathways associated with the development of PTC. We imply that the presence of certain genetic aberrations (e.g., BRAF V600E mutation) is associated with the activity of FRMD5. Methods: The studies were conducted on TPC1 and BCPAP (BRAF V600E) model PTC-derived cells. Transfection with siRNA was used to deplete the expression of FRMD5. The mRNA expression and protein yield were evaluated using RT-qPCR and Western blot techniques. Proliferation, migration, invasiveness, adhesion, spheroid formation, and survival tests were performed. RNA sequencing and phospho-kinase proteome profiling were used to assess signaling pathways associated with the FRMD5 expressional status. Results: The obtained data indicate that the expression of FRMD5 is significantly enhanced in BRAF V600E tumor specimens and cells. It was observed that a drop in intracellular yield of FRMD5 results in significant alternations in the migration, invasiveness, adhesion, and spheroid formation potential of PTC-derived cells. Importantly, significant divergences in the effect of FRMD5 depletion in both BRAF-wt and BRAF-mutated PTC cells were observed. It was also found that knockdown of FRMD5 significantly alters the expression of multidrug resistant genes. Conclusions: This is the first report highlighting the importance of the FRMD5 protein in the biology of PTCs. The results suggest that the FRMD5 protein can play an important role in controlling the metastatic potential and multidrug resistance of thyroid tumor cells.

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